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Biomedical subjects

P C Fitzgerald

Publications and source records attributed to P C Fitzgerald.

7 recordsLinked to original sources

Impact of the initial doses of rocuronium and pancuronium on subsequent maintenance for neuromuscular block.

PURPOSE: To determine the impact of the neuromuscular blocking agent given for intubation on the duration of effect of multiple maintenance doses of pancuronium and rocuronium. METHODS: Seventy-eight subjects were randomly assigned to receive one of four dosing combinations for intubation and neuromuscular maintenance: rocuronium for intubation and maintenance, rocuronium for intubation and pancuronium for maintenance, pancuronium for intubation and rocuronium for maintenance, or pancuronium for both. Each time that the first twitch response returned to 25% of the baseline value, the duration of the dose was determined and another maintenance dose was administered. The duration of action of the maintenance doses was compared between the groups. RESULTS: Twitch suppression from the first maintenance dose was shorter for subjects who received rocuronium for both doses (Group RR) compared with that for subjects that received pancuronium (Groups PR & PP) as their intubation dose (17.6 vs 34 & 59.8 min, respectively, P < 0.05). Subjects who received rocuronium followed by pancuronium (Group RP) showed a shorter duration of twitch suppression after the first maintenance dose than the group that received pancuronium for both doses (Group PP) (21.3 vs 59.8 min, P < 0.05). By the third maintenance dose, the influence of the intubating dose on the maintenance dose duration had essentially diminished. CONCLUSIONS: For combinations of rocuronium and pancuronium, the duration of twitch suppression after a maintenance dose is only dependent on the first agent given for the first two maintenance doses administered.

Adolescent↗

The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment.

UNLABELLED: Dexmedetomidine, an alpha2-adrenergic agonist with sedative and analgesic properties, is mainly cleared by hepatic metabolism. Because the pharmacokinetics of dexmedetomidine have not been determined in humans with impaired renal function, we studied them in volunteers with severe renal disease and in control volunteers. Six volunteers with severe renal disease and six matched volunteers with normal renal function received dexmedetomidine, 0.6 microg/kg, over 10 min. Venous blood samples for the measurement of plasma dexmedetomidine concentrations were drawn before, during, and up to 12 h after the infusion. Two-compartmental pharmacokinetic models were fit to the drug concentration versus time data. We also determined its hemodynamic, respiratory, and sedative effects. There was no difference between Renal Disease and Control groups in either volume of distribution at steady state (1.81 +/- 0.55 and 1.54 +/- 0.08 L/kg, respectively; mean +/- SD) or elimination clearance (12.5 +/- 4.6 and 8.9 +/- 0.7 mL x min(-1) x kg(-1), respectively). However, elimination half-life was shortened in the Renal Disease group (113.4 +/- 11.3 vs 136.5 +/- 13.0 min; P < 0.05). A mild reduction in blood pressure occurred in most volunteers. Although most volunteers were sedated by dexmedetomidine, renal disease volunteers were sedated for a longer period of time. IMPLICATIONS: The pharmacokinetics of dexmedetomidine in volunteers with severe renal impairment differed little from those in volunteers with normal renal function. In addition, there were no clinically significant differences in the hemodynamic responses to dexmedetomidine. However, dexmedetomidine resulted in more prolonged sedation in subjects with renal disease.

Adrenergic alpha-2 Receptor Agonists↗

Is an infusion pump necessary to safely administer remifentanil?

UNLABELLED: We sought to determine if remifentanil could be administered as safely and effectively from an IV drip as from a calculator pump, because not all anesthesiologists have access to a calculator pump. Forty healthy adults undergoing outpatient knee arthroscopy were premedicated with midazolam, 2 mg. Total IV anesthesia was induced with propofol by bolus (2 mg/kg) and maintained by a continuous infusion of propofol and remifentanil. On a randomized, double-blinded basis, they received, IV, either remifentanil (50 microg/mL) by syringe from an infusion pump or from a bag of saline containing remifentanil 20 microg/mL through a minidrip set. The remifentanil infusion syringe pump rate was 0.4 microg. kg(-1). min(-1) until skin incision and then 0.2 microg. kg(-1). min(-1), whereas that from the bag/minidrip set was set to approximate the delivery rate from the pump. Both a syringe pump and bag/minidrip set infusion were administered to each patient but only one contained remifentanil, that one being determined in a randomized, double-blinded manner. There were no differences in demographic data, time to recovery of open eyes, response to command, ability to speak (approximately 7 min), total dose and time of administration of propofol and remifentanil, the incidence of intraoperative hypotension and bradycardia, and postoperative shivering. We demonstrated that remifentanil can be administered as safely and effectively from a bag with a minidrip set as from a syringe in a calculator infusion pump, provided the anesthesiologist is paying attention to the drip rate from the bag. IMPLICATIONS: Because remifentanil is rapidly degraded in the body, it can be safely and effectively administered from a bag through a minidrip set. We showed that there was no difference with this less expensive method of administration than from the more precise method of a calculator infusion pump.

Adolescent↗

Effect of dexmedetomidine on the minimum alveolar concentration (MAC) of sevoflurane in adults age 55 to 70 years.

STUDY OBJECTIVE: To determine the effect of two target dexmedetomidine infusions (0.3 ng/ml and 0.6 ng/ml) on the minimal alveolar concentration (MAC) of sevoflurane in adults age 55 to 70 years. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: University-affiliated hospital. PATIENTS: 45 ASA physical status I and II adults, age 55 to 70 years, undergoing elective surgery with at least a 3 inch skin incision. INTERVENTIONS: Patients were given a dexmedetomidine or placebo infusion for at least 15 minutes before anesthetic induction with sevoflurane in oxygen by face mask. After tracheal intubation, a target sevoflurane concentration was maintained for 15 minutes while the dexmedetomidine or placebo infusion continued to run. MEASUREMENTS AND MAIN RESULTS: At the time of skin incision, two observers independently determined movement or nonmovement to the incision. Blood samples for dexmedetomidine were taken before the infusion and at the time of skin incision. The dexmedetomidine plasma concentrations were 0 before infusion with all treatment groups. At the time of incision, they were 0 in the placebo group, 0.39 +/- 0.13 ng/ml in the 0.3 ng/ml target group, and 0.7 +/- 0.13 ng/ml in the 0.6 ng/ml target group. The MAC of sevoflurane was 1.83% in the placebo group, 1.78% in the 0.3 ng/ml target dexmedetomidine group, and 1.51% in the 0.6 ng/ml target dexmedetomidine group. CONCLUSIONS: Dexmedetomidine 0.7 ng/ml decreased the MAC of sevoflurane by 17%, whereas there was no difference between the placebo and the dexmedetomidine 0.39 ng/ml group.

Adrenergic alpha-Agonists↗

Cloning and characterization of a potentially protective chitinase-like recombinant antigen from Wuchereria bancrofti.

While there is no direct evidence demonstrating the existence of protective immunity to Wuchereria bancrofti infection in humans, the presence of individuals, in populations in areas where infection is endemic, with no clinical evidence of past or current infection despite appreciable exposure to the infective larvae, suggests that protective immunity to filarial parasites may occur naturally. Earlier work indicated that such putatively immune individuals generated antibodies to a 43-kDa antigen from larval extracts of the related filarial parasite Brugia malayi that was recognized by only 8% of the infected population. With rabbit antiserum raised against this 43-kDa antigen, this current study identified a recombinant clone, WbN43, with an insert size of 2.3 kb, from a W. bancrofti genomic expression library. The recombinant fusion protein was differentially recognized by the putatively immune individuals but not by the infected patients. The coding sequence (684 bp) from the 5' end had significant sequence similarity to chitinases from Serratia marcescens, Bacillus circulans, Streptomyces plicatus, and B. malayi. Peptide sequencing of the expressed product also defined a chitinase-like sequence. Molecular characterization indicated WbN43 to be a low-copy-number gene, with expression predominantly in infective larvae and microfilariae but not in adult parasites.

Adult↗

Polyethenoadenosine phosphate as a fluorogenic substrate for barnase.

Polyethenoadenosine phosphate is rapidly hydrolyzed by barnase with an accompanying large increase in fluorescence. At pH 8, 0.2 M ammonium acetate, the initial rate of fluorescence increase is proportional to barnase concentration and thus provides an excellent quantitative assay for its activity. The preparation and use of this substrate in the barnase assay is presented in detail.

Bacterial Proteins↗

Characterization of a muscle-associated antigen from Wuchereria bancrofti.

A recombinant clone, WbN1, isolated from a genomic expression library of Wuchereria bancrofti and showing restricted specificity at the DNA level (Southern and PCR analyses) for Wuchereria bancrofti and Brugia malayi has been previously described. Sequence analysis of WbN1 indicated that it had notable similarity to myosin. Further characterization using in situ hybridization has localized the mRNA in the muscle of the adult parasite and in the microfilariae. Rabbit polyclonal antiserum, raised against the recombinant WbN1 fused to the maltose-binding protein, recognized a 200-kDa polypeptide in immunoblots containing B. malayi antigen extracts. The same antibody also recognized myosin extracted from Brugia pahangi, Onchocerca volvulus, and Caenorhabditis elegans. Localization using the rabbit antiserum revealed the presence of the antigen in the adult muscle tissue and in the microfilariae; the same antibody inhibited the binding of a monoclonal antibody 28.2 (directed toward MHC B of C. elegans myosin) to the recombinant WbN1 antigen and also to purified C. elegans myosin. Based on homology data, structural location, competitive ELISA, and immunoblot we conclude that WbN1 is related to myosin or a similar myofibrillar protein.

Amino Acid Sequence↗